Laka K, Mbita Z
Department of Biochemistry, Microbiology and Biotechnology, University of Limpopo, Polokwane, South Africa.
Front Mol Biosci. 2022 Jun 13;9:876213. doi: 10.3389/fmolb.2022.876213. eCollection 2022.
Current lung cancer treatment strategies are ineffective, and lung cancer cases continue to soar; thus, novel anticancer drugs and targets are needed, and medicinal plants are promising to offer better alternatives. This study was aimed at analysing two splice variants during the potential anticancer activities of () methanol and water extracts against different human lung cancer cell lines of varying mutation status, and these included mutant H1573 and mutant H1437 and -wild type (A549) cells. The anticancer activities of the extracts were assessed by establishing the cytotoxic effect and the apoptosis-inducing capacity of these extracts, using the MTT assay and Annexin V analysis, respectively, with the latter confirmed using fluorescence microscopy. The molecular mechanisms induced by these extracts were further evaluated using cell cycle analysis and RT-PCR. Both extracts demonstrated safety against noncancerous lung MRC-5 fibroblasts and exhibited significant anticancer potency ( < 0.001) against the H1437 (IC values: 62.50 μg/ml methanol extract and 125 μg/ml WE), H1573 (IC value: 125 μg/ml for both extracts) and A549 (IC value: 500 μg/ml ME). The water extract had no effect on the viability of A549 cells. Treated H1437 cells underwent -dependent apoptosis and S-phase cell cycle arrest while H1573 treated cells underwent -independed apoptosis and G0/G1 cell cycle arrest through upregulation of mRNA expression levels. The expression levels of , , and genes increased significantly ( < 0.001) following the treatment of H1573 cells with ME and WE. Treatment of H1437 cells with ME upregulated the , , and mRNAs. Our results indicate that the proliferative inhibitory effect of extracts on A549 and H1573 cells is correlated with the suppression of , and while that is not the case in H1437 cells. Thus, our results suggest that the dysregulation of anti-apoptotic molecules , , and in H1437 may play a role in cancer cell survival, which may consequently contribute to the development of -mutated non-small human lung cancer. Our results indicate that is a promising source of anticancer agents for the treatment of p53-mutant human non-small lung cancer cells than the p53-wild type human non-small lung cancer cells.
目前的肺癌治疗策略效果不佳，肺癌病例持续飙升；因此，需要新型抗癌药物和靶点，药用植物有望提供更好的选择。本研究旨在分析[植物名称]甲醇提取物和水提取物对不同突变状态的人肺癌细胞系（包括突变型H1573、突变型H1437和野生型A549细胞）潜在抗癌活性过程中的两种剪接变体。分别采用MTT法和膜联蛋白V分析，通过确定这些提取物的细胞毒性作用和诱导凋亡能力来评估提取物的抗癌活性，后者通过荧光显微镜确认。使用细胞周期分析和逆转录-聚合酶链反应进一步评估这些提取物诱导的分子机制。两种提取物对非癌性肺MRC-5成纤维细胞均显示出安全性，并对H1437（IC值：甲醇提取物62.50μg/ml，水提取物125μg/ml）、H1573（两种提取物的IC值均为125μg/ml）和A549（IC值：甲醇提取物500μg/ml）表现出显著的抗癌效力（P<0.001）。水提取物对A549细胞的活力没有影响。经处理的H1437细胞经历了p53依赖性凋亡和S期细胞周期阻滞，而经处理的H1573细胞通过上调p53 mRNA表达水平经历了p53非依赖性凋亡和G0/G1细胞周期阻滞。用甲醇提取物和水提取物处理H1573细胞后，p53、p21、Bax和Caspase-3基因的表达水平显著升高（P<0.001）。用甲醇提取物处理H1437细胞上调了p53、p21、Bax和Caspase-3的mRNA。我们的结果表明，[植物名称]提取物对A549和H1573细胞的增殖抑制作用与p53、p21和Bax的抑制相关，而在H1437细胞中并非如此。因此，我们的结果表明，H1437中抗凋亡分子p53、p21、Bax和Caspase-3的失调可能在癌细胞存活中起作用，这可能因此导致p53突变的非小细胞肺癌的发展。我们的结果表明，与p53野生型人非小细胞肺癌细胞相比，[植物名称]是治疗p53突变的人非小细胞肺癌细胞的有前景的抗癌剂来源。
